rs249153

Variant names:

• chr12-94930613-T-C
• rs249153
• ENST00000552205.6:n.258-2350A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000552205.6(NDUFA12):​n.258-2350A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,116 control chromosomes in the GnomAD database, including 4,286 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4286 hom., cov: 32)
• Consequence: NDUFA12 ENST00000552205.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48

Genes affected

NDUFA12 (HGNC:23987): (NADH:ubiquinone oxidoreductase subunit A12) This gene encodes a protein which is part of mitochondrial complex 1, part of the oxidative phosphorylation system in mitochondria. Complex 1 transfers electrons to ubiquinone from NADH which establishes a proton gradient for the generation of ATP. Mutations in this gene are associated with Leigh syndrome due to mitochondrial complex 1 deficiency. Pseudogenes of this gene are located on chromosomes 5 and 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA12	ENST00000552205.6	n.258-2350A>G		intron_variant	Intron 3 of 5	5		ENSP00000449144.2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34447 AN: 151994 Hom.: 4278 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.222

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.227 AC: 34467 AN: 152116 Hom.: 4286 Cov.: 32 AF XY: 0.223 AC XY: 16584 AN XY: 74380

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.0880

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.221

Alfa AF: 0.208 Hom.: 7113

Bravo AF: 0.231

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.020
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs249153; hg19: chr12-95324389;